There is considerable research on the effects of different rearing environments on the subsequent response to amphetamine. The most consistent finding in the literature is that rats raised in an enriched environment show enhanced sensitivity to the behavioral and neurochemical effects of amphetamine compared to rats raised in an impoverished environment. One mechanism proposed to explain this effect is via enhanced reversal of the dopamine transporter. In contrast to amphetamine, nicotine facilitates clearance of dopamine in terminal regions of the ascending dopaminergic pathways. Correspondingly, preliminary evidence in the present proposal shows that environmental enrichment confers a decrease in sensitivity to the locomotor stimulant effect of nicotine. Based on this differential sensitivity to the stimulant effect of nicotine, the experiments proposed in this application seek to assess the effects of differential rearing on the reinforcing efficacy of nicotine using an intravenous self-administration paradigm with rats. In addition, these experiments are also designed to elucidate the underlying mechanism(s) mediating the differential behavioral response to nicotine using in vivo chronoamperometric voltammetry to measure clearance of exogenously applied dopamine. Results from these experiments will provide preclinical evidence about the role of environmental enrichment during development in the etiology of tobacco dependence.